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International Journal of Bioprinting                                 Fluid mechanics of extrusion bioprinting




            nitrogen) or a mechanical system with a piston or screw to   form  of  an  intended  structure ;  this  is  characterized  by
                                                                                        38
            drive the liquid biomaterial.                      factors such as extrudability, filament fidelity, and structural
               While pneumatic-driven systems are widely used in   integrity. Printability depends on various parameters,
            most commercial bioprinters because of their simplicity,   including the viscosity and surface tension of the bioink,
            they possess a main drawback caused by gas compressibility.   the crosslinking time, as well as the surface properties of
                                                                                             36,39
            As a result, pneumatic-driven systems lack accurate control   the printing stage and printer nozzle.   Table 1 presents
            over the start and stop in extrusion or printing. This can   the printability criteria, the factors characterizing them,
            be offset by using a valve-based pneumatic system that   and how they affect printing outcomes. Regarding the
            facilitates high-precision extrusion by controlled pressure   extrudability, there are four typical cases for the extrusion
            and pulse frequency. 31,32  Additionally, the pneumatic-  of bioinks (Figure 1): (i) unextrudable, (ii) discontinuous
            driven system is not suitable for printing highly viscous   (dripping),  (iii)  continuous  but  uncontrollable  (with
            bioinks,  which requires  high  pressures  and  may  lead  to   gobbling drop 52,53 ), and (iv) continuous and controllable
                                                                      38
            related issues. 33                                 (jetting).  These cases can be recognized by comparing the
                                                               effective forces on the flow of bioink. To successfully extrude
               The piston- and screw-driven systems are more   bioink from the nozzle, the inertial force (characterizing
            accurate in extrusion or printing as the linear displacement   the acceleration of the fluid) should dominate the capillary
            of the piston or rotation of the screw can be accurately   force from the surface tension of the bioink that tends to
            controlled compared to the gas pressure in the pneumatic-
            driven system.  Moreover, both piston- and screw-driven   keep it attached to the nozzle.
                       34
            systems are good for printing high-viscosity bioinks,    The entire extrusion bioprinting process occurs within
                                                         35
            though it has been reported that the screw-driven system   the laminar flow regime, characterized by low Reynolds
            generally induces more cell damage compared to the   number (Re). Reynolds number is a dimensionless
            pneumatic-driven system. 36                        quantity that compares inertial and viscous forces in the
                                                               flow. For the flow of a Newtonian fluid inside a needle, Re
            2.2. Printability                                  is defined as :
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            During the  extrusion bioprinting  process, each  layer
            is stacked on top of the previous one to construct a 3D
            scaffold. To ensure the stability of the printed construct,      Re =  ρUd                     (I)
            the filaments need to solidify after being deposited on                η
            the printing stage. This solidification process is achieved
            through a crosslinking process, which can be either physical   where   and  h represent the density and dynamic
            or chemical.  However, the time required for crosslinking   viscosity of the fluid, respectively, d is the diameter of the
                      36
                                                                         -
            can pose challenges. During gelation, the bioink (in liquid   needle, and U the average velocity of the flow inside the
            form) may flow and spread on the printing stage, causing   needle. Due to the relatively high viscosity, the small size of
            deformations and deviations from the intended geometry.   the dispensing needle, and the slow velocity of the bioink
            This deviation from the designed structure is characterized   during the extrusion, extrusion bioprinting typically
            by printability. In some cases, the flow of the deposited   exhibits extremely low Re. This results in a special laminar
            bioink can even lead to the collapse of the entire structure,   flow regime known as creeping flow, characterized by the
            rendering it unprintable.  Printability significantly affects   dominance of viscous forces,  facilitating the smooth
                                36
                                                                                        54
            the mechanical and biological properties of the printed   deposition of filaments. Another important parameter in
            construct, such as its mechanical strength and cellular   extrusion bioprinting is the Weber number, which is the
            functionality.  To evaluate printability, it is common   ratio of inertial to capillary forces, presented as :
                      6–8
                                                                                                    54
            to analyze the differences between the printed construct
            and  the  intended  design,  considering  factors  such  as               2
            filament diameter and pore size.  These evaluations can be        We =  ρURi                   (II)
                                     37
            qualitative, relying on visual observations, or quantitative,            ζ
            involving  the  use  of  numerical  indices.   There  are
                                               37
            various definitions of printability in the literature, 38,39    where ρ is bioink density, R is the internal radius of
                                                                                         i
            each considering printability from different perspectives   the nozzle, and z denotes the surface tension of the bioink.
            to explain the ability to print a 3D construct that closely   For a given nozzle radius and bioink properties, the Weber
            matches  the  one  designed  in  computer-aided design   number is determined by the flow rate, which depends on
            (CAD) software. In this review, we adopt the definition of   the dispensing force applied by the driving mechanism to
            printability as the capability to create and uphold the 3D   the bioink.


            Volume 10 Issue 6 (2024)                       116                                doi: 10.36922/ijb.3973
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